This application addresses broad Challenge Area (06), Enabling Technologies, Topic 06-DK-104 Enabling technology for the prevention and treatment of diseases within the NIDDK mission. Priority areas include, for example: Improvement of medical devices such as...lithotriptors to minimize complications of procedures. Shock Wave Lithotripsy (SWL) is the most common treatment for kidney stones in the size range from about 2 - 20 mm: Kidney stones afflict 13% of men and 7% of women in the U.S. and these numbers are rising. The prevalence of kidney stones varies dependent on race, sex, age, and geographic location;however, stone formers can be any age, and many develop multiple stones at a time. Some stones pass spontaneously;however, those that don't pass account for over 2 million outpatient treatments and 1% of all hospitalizations annually in the U.S. In most lithotripters, shock waves generated outside the body are focused to a fixed location. The patient, usually under anesthesia or conscious sedation, is positioned with the stone within this focal zone. Between 1500 and 4000 shock waves are applied at about 2 Hz (range 1-4 Hz). The shock waves travel through water into the body. All current lithotripters have the SW source enclosed in a water-filled pillow that is coupled to the patient's skin. Treatment outcome is measured by stone-free rates after 1 to 3 months, and by re-treatment rates. Stone-free rates range from 40-90% with different machines;newer machines have lower stone-free rates and higher re-treatment rates. Although lithotripsy still accounts for more than half of all treatments for stone disease, it is gradually being replaced by minimally-invasive procedures, such as ureteroscopy and percutaneous nephrolithotomy. These more invasive procedures are likely the result of newer commercial versions of lithotripters having higher shock wave (SW) amplitudes and smaller focal volumes. These higher amplitudes and smaller foci often result in less efficient stone comminution and more tissue damage. Lithotripsy causes acute tissue injury that can lead to chronic adverse effects. The acute injury to kidney tissue is primarily a hemorrhagic lesion that is dependent on the SW dose. Studies in a porcine animal model show hemorrhage occupies 0.3% of the functional renal volume following 1000 SWs, 6.1% following a standard clinical dose of 2000 SWs, and 13.8% after 8000 SWs. The response is highly dependent on dose but is nonlinear, with the greatest injury occurring between 1000 and 2000 SWs. Our research has demonstrated that much of this reduced effectiveness of lithotripters is due to poor targeting and to limited feedback on the progress of the treatment. In particular, with more concentrated focal volumes, and limited accommodation for respiration, it is not uncommon for more than half of the SWs delivered to completely miss the stone-and with these more intense SWs-increased tissue damage. Additionally, because there is limited ability of conventional lithotripters to determine when the stone is sufficiently fragmented, it is often standard practice to deliver a full dose of SWs, even though the stone may be fully fragmented at much lower doses. In this application, we propose to improve lithotripters by developing engineering concepts and methodologies that enable more precise detection and localization of the stone, as well as real-time targeting and stone comminution-monitoring approaches. By improving targeting, and providing real-time feedback to the urologist, it is likely that lithotripters can realize greatly improved patient outcomes. The specific devices and methodologies to be developed in this effort will be tested on a porcine animal model as well as in ongoing human treatments. Successful accomplishment of the tasks outlined in this proposal will have potential for rapid incorporation into commercial lithotripters. PUBLIC HEALTH RELEVANCE: Shock Wave Lithotripsy (SWL) is the most common treatment for kidney stones in the size range from about 2 - 20 mm: Kidney stones afflict 13% of men and 7% of women in the U.S. and these numbers are rising. Although lithotripsy still accounts for more than half of all treatments for stone disease, it is gradually being replaced by minimally- invasive procedures, such as ureteroscopy and percutaneous nephrolithotomy, mostly because new generation lithotripters are less effective at stone fragmentation and induce additional tissue damage. The goal of this proposal is to provide immediate feedback to the urologist during lithotripsy treatment that will improve stone break-up and reduce kidney damage.